Neuroscience
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Drug addiction is associated with dysfunction in the medial prefrontal cortex (mPFC). However, the modifications of neuronal activity in mPFC underlying the reinforcing properties of addictive drugs are still unclear. Here we carried out single-unit recording experiments to study the neuronal activity in the prelimbic (PL) cortex of anesthetized rats, after expression of locomotor sensitization to amphetamine. ⋯ Moreover, in control rats, acute amphetamine decreased burst rate, whereas in sensitized rats acute amphetamine increased burst rate. These findings indicate that amphetamine sensitization renders mPFC neurons hyperexcitable. Taken together, these data support the hypothesis that early withdrawal is associated with an increase in the activity of the mPFC, which could strengthen the PL-Nucleus Accumbens connection, thus facilitating amphetamine-induced locomotor sensitization.
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The present study investigated the effects of chronic social defeat stress on several behavioral parameters, and the expression of dopaminergic markers, i.e., dopamine D1 receptors (D1Rs), dopamine D2 receptors (D2Rs), and dopamine and cyclic adenosine 3',5'-monophosphate-regulated phosphoprotein-32 (DARPP-32), in the prefrontal cortex (PFC), amygdala (AMY), and hippocampus (HIP) of mouse brains. After 10days of social defeat stress, the defeated mice were divided into two groups: one group underwent a series of behavioral tests. The other group was sacrificed on the 11th day and tissue samples were collected for Western blotting. ⋯ No significant differences in D1Rs and D2Rs expression were shown between defeated and control mice in any area studied. A significantly increased expression in total DARPP-32, and phospho-DARPP-32 was observed in the PFC or AMY of defeated mice. These data suggest that alterations in dopaminergic markers may be involved in anxiety- and depression-like behaviors, and cognitive impairment induced by social defeat stress.
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Structural changes that alter hippocampal functional circuitry are implicated in learning impairments, mood disorders and epilepsy. Reorganization of mossy fiber (MF) axons from dentate granule cells is one such form of plasticity. Increased neurotrophin signaling is proposed to underlie MF plasticity, and there is evidence to support a mechanistic role for brain-derived neurotrophic factor (BDNF) in this process. ⋯ No evidence of MF sprouting was seen in the inner molecular layer. Additional stereological analyses demonstrated significant increases in molecular layer (ML) volume in TgBDNF mice at both ages, as well as an increase in granule cell number by 8months of age. Collectively, these results indicate that sustained increases in endogenous BDNF modify dentate structural organization over time, and may thereby contribute to the development of pro-epileptic circuitry.
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Comparative Study
GAD65/GAD67 double knockout mice exhibit intermediate severity in both cleft palate and omphalocele compared with GAD67 knockout and VGAT knockout mice.
Inhibitory neurotransmitters, γ-aminobutyric acid (GABA) and glycine, are transported into synaptic vesicles by the vesicular GABA transporter (VGAT). Glutamate decarboxylase (GAD) is a GABA-synthesizing enzyme and two isoforms of GAD, GAD65 and GAD67 are encoded by two independent genes. There was virtually no GABA content in GAD65/GAD67 double knockout (GADs DKO) mouse brains. ⋯ The severity of cleft palate and omphalocele was evaluated by elevation of palate shelves and size and liver inclusion of omphalocele, respectively. We observed that the phenotypes of cleft palate and omphalocele in GADs DKO mice were more and less severe than those in GAD67 KO and VGAT KO mice, respectively. These results indicate the significant contribution of not only GAD65-mediated GABAergic but also glycinergic transmissions to both palate and abdominal wall formations.
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Pudendal nerve-spinal pathways are involved in urethrogenital sensation, pain and sexual activity. However, details of these pathways and their modulation are unclear. We examined spinal pathways activated by the urethrogenital reflex (UGR) and visualized by c-Fos immunoreactivity in reflexly activated neurons within spinal cord. ⋯ However, after L4 transection, UGR generation was associated with a four- to sixfold increase in c-Fos-expressing neurons in lateral horn (LH) and central canal areas at S2, and but only 20-30% increase at L3. Thus, UGR activates preganglionic neurons projecting to pelvic viscera in both sacral and lumbar spinal cord. The reflex also must activate ascending and descending spinal inhibitory circuits that suppress c-Fos-expression in neurons at both sacral and lumbar spinal levels.